Rational Development of a Novel Attenuated Rift Valley Fever Virus Vaccine
新型裂谷热病毒减毒疫苗的合理研制
基本信息
- 批准号:9386475
- 负责人:
- 金额:$ 23.25万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2017
- 资助国家:美国
- 起止时间:2017-05-25 至 2019-04-30
- 项目状态:已结题
- 来源:
- 关键词:AffectAfricaAfrica South of the SaharaAgeAgricultureAnimalsAntigensArthralgiaAttenuatedAttenuated VaccinesBioterrorismBunyaviridaeCategoriesCattleCellsCellular MembraneCenters for Disease Control and Prevention (U.S.)Cessation of lifeCodon NucleotidesCountryCulicidaeCultured CellsDataDevelopmentDiseaseDisease OutbreaksEconomicsEncephalitisEndemic DiseasesEpidemicEpitopesExhibitsFamilyFeverFluorouracilGeneral PopulationGeneticGenomeGenus PhlebovirusGlycoproteinsHeadacheHealth StatusHumanHumoral ImmunitiesImmune responseImmunityImmunizationImmunizeImmunocompromised HostImpairmentIndividualInvadedLiteratureLivestockMass VaccinationsMediatingMovementMusMutationMyalgiaNational Institute of Allergy and Infectious DiseaseNeuraxisNeurologic SignsNorth AmericaOrthobunyavirusPanicPatientsPeptidesPhotophobiaPlayPopulationProductionPropertyProteinsPublic HealthRNAResearchRetinalRetinal VasculitisRift Valley fever virusRoleRuminantsSCID MiceSafetySerial PassageSerologicalSheepTestingTimeVaccinationVaccinesViralViral Envelope ProteinsViral Hemorrhagic FeversViral PhysiologyViral Structural ProteinsVirionVirusVirus DiseasesVirus ReplicationVirus-like particleVisual impairmentWild Animalsbasedesigneconomic impactgenomic RNAimmunogenicimmunogenicityimprovedintraperitonealmaculamembermouse modelmutantneurovirulenceneutralizing antibodynovelpathogenpreventprogramsprotective efficacysafety testingvaccine candidatevectorviral transmissionvirus envelope
项目摘要
Abstract
Rift Valley fever virus (RVFV), a prototypical Phlebovirus (family Bunyaviridae), belongs to the
NIAID Category A list of pathogens and the CDC list of potential bioterrorism agents. RVFV
causes a disease that is endemic in sub-Saharan Africa and can emerge in explosive,
mosquito-borne epidemics decimating herds of sheep and cattle, resulting in enormous
economic losses. In humans, RVFV infection may cause hemorrhagic fever, encephalitis, and
retinal vasculitis. Many different mosquitoes, including several native to North America, are
competent vectors for RVFV transmission. Thus, the introduction of RVFV into North America
would likely cause panic in the general population, and the effects on livestock could have a
devastating economic impact. Induction of a humoral immune response against the viral
envelope proteins is necessary and sufficient to provide protection against RVFV. Currently,
there is no RVFV vaccine suitable for mass human vaccination programs. The MP-12 strain,
which was obtained by 12 serial passages of the wild-type RVFV strain ZH548 in the presence
of 5-fluorouracil, is markedly attenuated in mice but retains its immunogenicity. However,
intraperitoneal inoculation of MP-12 into young mice or SCID mice results in efficient virus
replication in the animals’ central nervous system. The neuroinvasiveness and neurovirulence
potential of MP-12 is a matter of concern when considering the mass vaccination of the general
public, especially, in immunocompromised individuals. The present application proposes the
development of a novel and safer MP-12-derived vaccine candidate having several mutations
that selectively abolish specific functions of viral envelope glycoproteins and cause a higher
expression level of neutralizing epitopes in infected cells. We will test the hypothesis that this
MP-12-based vaccine candidate exhibits a better safety profile than MP-12 in mice but still
retains its immunogenicity and protective efficacy. In this proposal, we will examine its genetic
stability in cultured cells and assess its safety, immunogenicity, and protective efficacy by using
mouse models.
抽象的
裂谷热病毒(RVFV)是一种典型的白蛉病毒(布尼亚病毒科),属于
NIAID A 类病原体清单和 CDC 潜在生物恐怖主义病原体清单。
引起一种在撒哈拉以南非洲地区流行的疾病,并且可能呈爆炸性、
蚊子传播的流行病导致羊群和牛群大量死亡,造成巨大损失
在人类中,RVFV 感染可能导致出血热、脑炎和
许多不同的蚊子,包括几种原产于北美的蚊子,都可以引起视网膜血管炎。
RVFV 传播的有效载体因此,RVFV 被引入北美。
可能会引起普通民众的恐慌,并对牲畜产生影响
诱导针对病毒的体液免疫反应。
目前,包膜蛋白对于提供针对 RVFV 的保护是必要且充分的。
没有适合大规模人类疫苗接种计划的 RVFV 疫苗,
这是通过野生型 RVFV 株 ZH548 在存在下连续传代 12 次获得的
5-氟尿嘧啶的免疫原性在小鼠体内显着减弱,但保留了其免疫原性。
将 MP-12 腹膜内接种到幼年小鼠或 SCID 小鼠中可产生有效的病毒
动物中枢神经系统的复制 神经侵袭性和神经毒力。
在考虑对一般人群进行大规模疫苗接种时,MP-12 的潜力是一个值得关注的问题
公众,尤其是免疫受损的个体。
开发一种新型且更安全的 MP-12 衍生候选疫苗,具有多种突变
选择性地消除病毒包膜糖蛋白的特定功能并导致更高的
我们将检验感染细胞中中和表位的表达水平。
基于 MP-12 的候选疫苗在小鼠中表现出比 MP-12 更好的安全性,但仍然
保留其免疫原性和保护功效在本提案中,我们将检查其遗传。
培养细胞的稳定性,并通过使用评估其安全性、免疫原性和保护功效
鼠标模型。
项目成果
期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
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Shinji Makino其他文献
Shinji Makino的其他文献
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{{ truncateString('Shinji Makino', 18)}}的其他基金
Mechanism of viral RNP recognition by the envelope glycoprotein and its role in RNA segment packaging in Rift Valley Fever phlebovirus
裂谷热白蛉病毒包膜糖蛋白识别病毒RNP的机制及其在RNA片段包装中的作用
- 批准号:
10057583 - 财政年份:2020
- 资助金额:
$ 23.25万 - 项目类别:
Mechanism of viral RNP recognition by the envelope glycoprotein and its role in RNA segment packaging in Rift Valley Fever phlebovirus
裂谷热白蛉病毒包膜糖蛋白识别病毒RNP的机制及其在RNA片段包装中的作用
- 批准号:
10188412 - 财政年份:2020
- 资助金额:
$ 23.25万 - 项目类别:
Interplay between coronaviruses and nonsense-mediated mRNA decay pathway
冠状病毒与无义介导的 mRNA 衰减途径之间的相互作用
- 批准号:
10358595 - 财政年份:2020
- 资助金额:
$ 23.25万 - 项目类别:
Interplay between coronaviruses and nonsense-mediated mRNA decay pathway
冠状病毒与无义介导的 mRNA 衰减途径之间的相互作用
- 批准号:
10614383 - 财政年份:2020
- 资助金额:
$ 23.25万 - 项目类别:
Development of Safer,Live Attenuated Rift Valley Fever Vaccines
开发更安全的裂谷热减毒活疫苗
- 批准号:
9091408 - 财政年份:2015
- 资助金额:
$ 23.25万 - 项目类别:
New Paradigm for Host and Viral Gene Regulation by MERS Coronavirus nsp1
MERS 冠状病毒 nsp1 宿主和病毒基因调控的新范式
- 批准号:
9189963 - 财政年份:2015
- 资助金额:
$ 23.25万 - 项目类别:
Development of a Novel Rift Valley Fever Virus Vaccine
新型裂谷热病毒疫苗的开发
- 批准号:
8604678 - 财政年份:2013
- 资助金额:
$ 23.25万 - 项目类别:
Development of a Novel Rift Valley Fever Virus Vaccine
新型裂谷热病毒疫苗的开发
- 批准号:
8509347 - 财政年份:2013
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$ 23.25万 - 项目类别:
Analysis of Coronavirus-Host Cell Interactions
冠状病毒-宿主细胞相互作用分析
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Analysis of Coronavirus-Host Cell Interactions
冠状病毒-宿主细胞相互作用分析
- 批准号:
8888201 - 财政年份:2012
- 资助金额:
$ 23.25万 - 项目类别:
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